The present invention relates, generally, to the treatment of vascular disorders and, more particularly, to the treatment of aneurysms with radioactive intraluminal endovascular prosthesis.
While conventional bypass graft treatment of aneurysms has steadily improved, mortality rates continue to be relatively high in cases such as abdominal aortic aneurysms. These often asymptomatic aneurysms 15 of blood vessel 16, as shown in FIG. 1, generally progressively enlarge in most patients over time, increasing the risk of rupture. Traditional bypass grafts are then required which are extremely invasive and include all the risks of open surgeries such as paraplegia, renal insufficiency, and myocardial infarction. Moreover, even three (3) to five (5) years after these surgeries, complications may arise which include concomitant coronary atherosclerotic disease, graft infection, aortoenteric fistula, thromboembolish, and anastomotic aneurysms.
In the recent past, more innovative approaches have evolved for the treatment of aneurysms. For example, DACRON(copyright) grafts, endovascular stent grafts and covered stents (referred heretofore generally as xe2x80x9cstent graftsxe2x80x9d), which have rapidly developed in an effort to expand stent technology, may be employed as a means of aneurysm treatment. These hybrid devices combine graft material with a stent or stent-like device to provide an expandable, stent-like structure having an impervious luminal surface.
These combination of features, once implanted, are very conducive to achieve endovascular exclusion of aneurysms. Typically, a graft material is mounted to and positioned along an exterior circumferential surface and/or the interior circumferential surface of the prosthesis in a manner forming an endovascular, blood impervious lumen therethrough. A proximal end of the graft is preferably endovascularly positioned just upstream from the vascular disorder while a distal end thereof terminates at a position just downstream thereof. As the proximal end and the distal end of the stent graft become anastomosed with the vessel wall, the vascular disorder becomes endovascularly excluded from the blood flow while the is stent graft impervious lumen maintains vessel patency
Upon proper endovascular deployment and seal formation of the stent, cell matrix formation and tissue healing may commence in the aneurysmal sac and on the luminal surface. For example, in the aneurysmal sac between stent graft and the vascular wall, the residual blood clotting and inflammatory response cause cellular proliferation and connective formation, forming a matrix that may seal the sac. In addition to the sealing, the resulted wall, which is a combination of prosthesis, connective tissue matrix, and arterial wall provides a conduit support of proper hemodynamic blood flow.
Intraluminally, thromboembolic processes will occur on the luminal surface of the graft/stent. Briefly, during this thrombotic phase, platelets and blood clots adhere to the surface to form a fibrin rich thrombus. Endothelial cells then appear, followed by intense cellular infiltration. Finally, during the proliferative phase, actin-positive cells colonize the residual thrombus, resorbing the thrombus.
The primary problem associated with this technique is the time period required for endovascular sealing and repair of the aneurysmal sac. Tissue response to injuries of this nature are generally on the order of a few months to years. This is especially true for the luminal surface of the graft material where organized thrombus formation may be difficult to achieve. Such endothelial cell growth to line the lumen of the stent graft may require years of healing or may never be fully completed.
Accordingly, several clinical complications may result due to improper delayed cellular healing. One of the most prevalent problems, aortoentenic fistula, arises when the seal integrity between the vessel wall and the proximal end of the stent graft is compromised due to slow thrombus formation and incomplete tissue growth. Such upstream, proximal seal breaches cause blood infiltration through the incomplete anastomosis that may lead to abdominal blood loss. Stent grafts efficiency and effectiveness are substantially reduced since the luminal surface is not re-endothelialized, exposing the foreign surface to the risk of thrombosis and its complications.
There is a need, therefore, to increase the effectiveness and efficiency of the stent graft to reduce the time period for vascular repair.
Accordingly, a method is provided for promoting and increasing the rate of at least one of thrombus formation and proliferative cell growth of a selected region of cellular tissue. The method includes the step of endovascularly irradiating of the selected region endovascular radiation, having a dose range of about 1 Gy to about 600 Gy at a low dose rate of about 1 cGy/hr to about 320 cGy/hr, to promote thrombus proliferation followed by cellular proliferation of the affected selected region. Preferably, the dose of endovascular radiation is about 1 Gy to about 25 Gy at the graft surface, and at a low dose rate of about 1 cGy/hr to about 15 cGy/h. The selected region is preferably the luminal blood contents such as platelets, clotting proteins, and fibrin, while the target cells may include circulatory stem cells and cells from the adjacent connective tissue.
In one embodiment, the present method includes the step of positioning a deformable endovascular device, adapted to endovascularly emit the radioactive field, proximate the aneurysm. This step is performed by implanting the deformable endovascular device adjacent the aneurysm of the blood vessel. To generate the radioactive field and before the positioning step, the present invention includes the step of embedding radioactive material in the deformable endovascular device.
In another embodiment the embedding step further includes the step of: embedding a central portion of the endovascular prosthesis, sized to extend substantially adjacent the aneurysm when properly positioned, with a first radioactive activity generating the first named radiation acting upon the aneurysm; and embedding the end portions of the endovascular prosthesis, positioned on opposed sides of the central portion and extending beyond the upstream end and the downstream end of the aneurysm, with a second radioactive activity generating a second radiation having a dosage adapted to decrease thrombus formation and/or cell proliferation of the affected regions flanking the aneurysm.
In still another embodiment, the method of the present invention includes the step of positioning an intra-luminal endovascular prosthesis in the vessel proximate the aneurysm; and deploying the endovascular prosthesis from a contracted condition to an expanded condition, wherein the endovascular prosthesis engages the interior walls of the blood vessel forming a void between the endovascular prosthesis and the aneurysm for receipt of the radioactive seeds therein and such that the radioactive seeds are substantially retained is the void by the endovascular prosthesis. In another method, radiosensitizers may be deposited within the void or the aneurysmal sac, or be inserted into the aneurysmal contents. These radiosensitizers will be made radioactive or activated through external beam radiation or endovascular irradiation.
In another aspect of the present invention, a proliferation device is provided for increasing the rate of proliferative cell growth and/or induce thrombus formation of a selected region of cellular tissue. The proliferation device includes a deformable endovascular device adapted for secured positioning adjacent to the selected region of cellular tissue, and a radioactive source. This source cooperates with the deformable endovascular device in a manner endovascularly irradiating the selected region with endovascular radiation, having a dose range of about 1 Gy to about 600 Gy at a low dose rate of about 1 cGy/hr to about 320 cGy/hr, to increase thrombus formation and/or cell proliferation of the affected selected region.
The radioactive source is provided by radioactive material embedded in the deformable endovascular device. In one embodiment, the deformable endovascular device is provided by radioactive coils, endovascularly irradiating the radiation, sized and dimensioned for receipt in a pseudoaneurysm. In another embodiment, for saccular or fusiform aneurysms, the deformable endovascular device is provided by a tubular-shaped intraluminal endovascular prosthesis radially expandable from a contracted condition and an expanded condition. In the contracted condition, percutaneous delivery into the blood vessel is enabled, and an expanded condition, the deformable endovascular device radially contacts the interior walls of the blood vessel for implanting thereto. In another method, the described endovascular sources can be radiosensitizers or radioactive sources that are coated with biologic factors such as growth factors, adhesion molecules, and organic matrix
The thrombus formation and/or cellular proliferation device further includes a tubular-shaped sheath device defining a lumen therethrough, and cooperating with the endovascular prosthesis to substantially prevent fluid communication between fluid flow through the lumen of the blood vessel and the aneurysm, while maintaining vessel patency. For the aneurysms, the prosthesis is sized and dimensioned to extend beyond an upstream end of the aneurysm and beyond a downstream end of the aneurysm each by at least about 1.0 mm when properly positioned in the vessel.